Influenza virus poses a major threat to human health. It also predisposes to superinfection of the respiratory tract (RT), most commonly by Streptococcus pneumonia, and is responsible for . significant morbidity and mortality, particularly in the young and elderly. B cells play a vital role in immunity to influenza virus, highlighted by the production of viral-neutralizing antibodies and in the efficacy of influenza vaccines. While it is appreciated that B cells play a critical role in the host response to influenza virus, less is known about the nature of the protective humoral response in the RT. Our project proposes to comprehensively analyze and compare the B cell response in the lung to influenza virus under conditions of viral infection with or without bacterial co-infection as well as vaccination. We hypothesize that the B cell response to influenza virus will have distinct signatures in these divergent contexts. Emphasis will be placed on features of the local RT immunity that promote anti-influenza B cell survival, maturation and differentiation. We will also identify the mechanisms that govern the development, recruitment and maintenance of plasma cells (PC) in the RT. While short-term PC may participate in rapid first line of host defense, long-term PCs and memory cells are critical for the development of lasting protection. By defining the anti-influenza response in situ where the virus infects lung epithelial cells, we may be better equipped to induce targeted mucosal protection through vaccination.